OBJECTIVEAdverse effects of hypercaloric, high-fructose diets on insulin sensitivity and lipids in human subjects have been shown repeatedly. The implications of fructose in amounts close to usual daily consumption, however, have not been well studied. This study assessed the effect of moderate amounts of fructose and sucrose compared with glucose on glucose and lipid metabolism.RESEARCH DESIGN AND METHODSNine healthy, normal-weight male volunteers (aged 21–25 years) were studied in this double-blind, randomized, cross-over trial. All subjects consumed four different sweetened beverages (600 mL/day) for 3 weeks each: medium fructose (MF) at 40 g/day, and high fructose (HF), high glucose (HG), and high sucrose (HS) each at 80 g/day. Euglycemic-hyperinsulinemic clamps with [6,6]-2H2 glucose labeling were used to measure endogenous glucose production. Lipid profile, glucose, and insulin were measured in fasting samples.RESULTSHepatic suppression of glucose production during the clamp was significantly lower after HF (59.4 ± 11.0%) than HG (70.3 ± 10.5%, P < 0.05), whereas fasting glucose, insulin, and C-peptide did not differ between the interventions. Compared with HG, LDL cholesterol and total cholesterol were significantly higher after MF, HF, and HS, and free fatty acids were significantly increased after MF, but not after the two other interventions (P < 0.05). Subjects’ energy intake during the interventions did not differ significantly from baseline intake.CONCLUSIONSThis study clearly shows that moderate amounts of fructose and sucrose significantly alter hepatic insulin sensitivity and lipid metabolism compared with similar amounts of glucose.

TSH concentrations are elevated in obese children but are not correlated with the amount of excess body weight or fat. During weight loss, independent of changes in body weight or composition, decreases in elevated serum TSH predict decreases in fasting insulin and HOMA. These findings suggest interventions that target high TSH concentrations during weight loss in obese subjects may improve insulin sensitivity.

Oxidative stress and low-grade systemic inflammation may contribute to the pathogenesis of obesity-induced comorbidities, including nonalcoholic fatty liver disease. Increasing intake of dietary antioxidants might be beneficial, but there are few data in obese children. To examine the effect of antioxidant supplementation on biomarkers of oxidative stress, inflammation, and liver function, we randomly assigned overweight or obese children and adolescents (n = 44; mean ± SD age: 12.7 ± 1.5 y) participating in a lifestyle modification program to a 4-mo intervention with daily antioxidants (vitamin E, 400 IU; vitamin C, 500 mg; selenium, 50 μg) or placebo. We measured anthropometrics, antioxidant status, oxidative stress (F(2)-isoprostanes, F(2)-isoprostane metabolites), inflammation, liver enzymes, fasting insulin and glucose, and lipid profile at baseline and endpoint. There was a significant treatment effect of antioxidant supplementation on antioxidant status [α-tocopherol, β = 23.2 (95% CI: 18.0, 28.4); ascorbic acid, β = 70.6 (95% CI: 51.7, 89.4); selenium, β = 0.07 (95% CI: 0.01, 0.12)] and oxidative stress [8-iso-prostaglandin F2α, β = -0.11 (95% CI: -0.19, -0.02)] but not on any of the inflammatory markers measured. There was a significant treatment effect on alanine aminotransferase [β = -0.13 (95% CI: -0.23, -0.03)], a trend toward a significant effect on aspartate aminotransferase [β = -0.04 (95% CI: -0.09, 0.01)], and no significant effect on γ-glutamyltransferase [β = -0.03 (95% CI: -0.11, 0.06)]. In summary, antioxidant supplementation for 4 mo improved antioxidant-oxidant balance and modestly improved liver function tests; however, it did not reduce markers of systemic inflammation despite significant baseline correlations between oxidative stress and inflammation. The study was registered at clinicaltrials.gov as NCT01316081.

Background: It is unclear whether high plasma leptin in obese individuals represents leptin resistance or whether individuals with marked reductions in leptin concentrations in response to weight loss may be at greater risk of regaining weight. Moreover, whether changes in leptin predict metabolic improvements during weight loss is uncertain. Objective: The objective was to prospectively examine associations between plasma leptin, body fat, and weight and metabolic risk factors in obese children during weight loss. Design: In obese children and adolescents [n = 203; mean age: 14.1 y, .98th body mass index (BMI) percentile for age and sex] participating in a 2-mo inpatient weight-loss program, we measured changes in body composition (by dual-energy X-ray absorptiometry), plasma leptin, insulin, and lipids. After discharge, anthropometric measures and plasma leptin were remeasured at 6 (n = 139) and 12 (n = 100) mo. Results: During the 2-mo program, mean (6SD) weight and fat loss were 13.9 6 4.0 kg and 9.2 6 2.5 kg, respectively; and mean plasma leptin decreased by 76%. Weight and fat loss were sustained, and no significant differences in BMI-SD score (SDS) or body composition were found between 12 and 2 mo. Baseline leptin was a negative predictor for percentage fat loss at 2, 6, and 12 mo (P , 0.05). The percentage change in leptin during the 2-mo intervention positively correlated with the relative change in fasting insulin, the relative change in LDL cholesterol at 2 mo, percentage fat loss, and change in BMI-SDS at 2 and 6 mo (P , 0.02). Conclusions: Even in obese children with strongly elevated baseline leptin, large leptin reductions that predict short-and long-term loss of body fat and improvements in lipids and insulin sensitivity can be achieved. Thus, increased plasma leptin in obese children may not necessarily reflect leptin resistance; many children appear to remain leptin sensitive at this age.Am J Clin Nutr 2011;93:695-702.